anti-TB Drug Treatment Research Articles

Evaluation of clinical outcomes of one-stage anterior and posterior surgical treatment for atlantoaxial tuberculosis complicated with neurological damage

BackgroundSurgical treatment is mainly used for atlantoaxial tuberculosis with neurological damage. However, the anatomic structure around the atlantoaxial joint is complex, and the position of vertebral body is deep, which increases the difficulty of the operation and it is challenging for the surgeon to develop surgical strategy. The purpose of this study was to evaluate the clinical outcomes of one-stage combined anterior and posterior surgical treatment approach for atlantoaxial tuberculosis with neurological impairment.MethodsFrom January 2005 to January 2015, 12 patients suffering from atlantoaxial tuberculosis with neurological impairment were surgically treated by one-stage combined anterior and posterior approach. Preoperative CT scanning and MRI imaging showed unilateral or bilateral lateral mass destruction of the atlas, and varying destruction degrees of odontoid process, loss of atlantoaxial stability, and tuberculosis focus into the spinal canal resulting in the corresponding spinal cord compression in all patients. The preoperative neurological classifications were Class C for 4 cases, D for 8 cases according to the American Spinal Injury Association (ASIA) system. Quadruple sensitive anti-TB drug treatment was used in all 12 patients preoperative and postoperative. Patients’ clinical symptoms and neurological function recovery were evaluated by comparing the Visual Analogue Scale (VAS) score, Neck Disability Index (NDI), Japanese Orthopedic Association (JOA) score and ASIA grading before operation and at the final follow-up.ResultsMean surgical duration was 263.3 ± 43.6 min. Intraoperative blood loss was averagely 529.2 ± 169.8 ml. The average fusion period was 7.3 ± 1.5 months. No instrumentation loosening, migration or breakage was observed during the follow-up of 6.5 ± 2.9 years. The VAS, NDI and JOA scores were significantly changed to 1.00 ± 0.95, 9.50 ± 3.34 and 15.42 ± 1.44 at last follow-up (P < 0.05). The neurological function of all 12 patients was recovered to Class E according to the ASIA grading system.ConclusionIn the treatment of atlantoaxial tuberculosis with neurological impairment, one-stage combined anterior and posterior surgical approach have the ability to complete debridement and decompression, and reconstruction of the stability of the upper cervical spine.

Antituberculosis Drugs Resistance and Treatment Outcomes Among Retreatment Patients in Guinea: A Five-Year Retrospective Cohort Study

Tuberculosis (TB) is a global outbreak whose drug resistance is a constant threat. This study aimed at describing anti-TB drugs resistance and treatment outcomes among retreatment TB patients in Guinea between 2008 and 2012. We conducted a retrospective cohort study with a sample of 558 patients aged of at least 10, who were admitted for TB retreatment and who were tested for anti-TB drugs susceptibility during the study period. Overall, 3187 retreatment TB patients were recorded from January 1, 2008 to December 31, 2012 in Guinea, of which 558 (17.5%) performed susceptibility testing to anti-TB drugs. We found overall resistance in 417 cases (74.7%) including 356 (85.4%) of multidrug resistance (MDR), 29 (6.9%) of monoresistance (isoniazid 2.9%, streptomycin 2.9%, rifampicin 0.9%, ethambutol 0.2%) and 32 (7.7% of polydrug resistance (isoniazid + streptomycin 4.3%, rifampicin + streptomycin 1.4%, isoniazid + ethambutol + streptomycin 1.0%, rifampicin + ethambutol + streptomycin 1.0%). Most of the patients (84.6%) with anti-TB drugs resistance were under 45 and labourers were mostly represented (27.8%) including drivers in majority (37.9%). MDR-TB incidence rate increased by 12.2% between 2008 (65.6%) and 2012 (77.8%), and the annual cure rate decreased gradually from 60.0% in 2009 to 45.7% in 2012. Among MDR-TB patients (n= 356), only 112 (31.5%) benefited from second-line treatment regimen, of which, 51.7% were cured, 6.3% completed treatment, 24.1% died, 6.3% were lost to follow-up and 11.6% were not evaluated. The cure rate was higher in HIV-negative patients (55.3%) than in those who were HIV-positive (35.3%) and the death rate was the highest (41.2%) in HIV-positive patients. Overall, treatment success rate was 58.0%. This study revealed a low rate of performing drug susceptibility testing, the gradual increase of the incidence of MDR-TB each year and the gradual decrease of cure rate from year to year. Besides, anti-TB drugs resistance concerned mostly drivers in our context. Prospective studies are needed for a deep understanding of the factors associated with these persistent challenges.

The Analysis of Safety and Effectiveness Using Allograft in the Treatment of Spinal Tuberculosis-A Multicenter Retrospective Study

To evaluate the clinical efficacy and fusion characteristics of allografts in spinal tuberculosis (TB). The research reviewed 1196 patients with spinal tuberculosis who received treatment at six hospitals from January 2000 to January 2016. A total of 623 patients who had spinal tuberculosis were included in the study. All patients underwent debridement, decompression, allograft bone grafting, and instrumentation. Postoperative treatment consisted of a combination of anti-TB drug treatment for 18 months and brace fixed braking for 3–9 months. Clinical outcome, laboratory indexes, and radiological results were analysed. The average follow-up time was 34.1 months (12–60 months). Pain was relieved postoperatively in all cases, and 87.8% of patients were painless at the final follow-up. The erythrocyte sedimentation rate (ESR) significantly decreased and returned to normal at the final follow-up. The fusion rate of allografts was 30.2% and 98.4% at the 9- and 12-month follow-ups, respectively. At the final follow-up, the fusion rate was 100%. The application of allografts in the surgical management of spinal tuberculosis is safe and effective. Allografts can replace autografts in surgeries for spinal tuberculosis.

The Effect of Complementary Vitamin D on Sputum Conversion in Pulmonary TB Patients

Background: Pulmonary TB is one of the most important health problems in Indonesia. The number of pulmonary TB patients ranked second after India. Vitamin D has a complex effect in the immune system. One of the effects of vitamin D is to stimulate the production of Cathelicidin which increases macrophage phagocytosis. This study aimed to analyze the effect of complementary vitamin D on sputum conversion in pulmonary tuberculosis patients. Subjects and Method: This study was a randomized controlled trial conducted at several health centers in Deli Serdang, North Sumatera, from November 2015 to June 2016. A total sample of 80 patients with positive acid-resistant bacilli (BTA) was selected for this study by consecutive sampling. The sample was allocated randomly into two groups: (1) TB drug group + 2.5 mg vitamin D; (2) TB drug group + placebo. The dependent variable was sputum conversion. The independent variable was complementary vitamin D. Pre and post vitamin D levels were examined by ELISA technique. Sputum conversion was examined by TB laboratory worker at the health center where patients received TB drug treatment. Difference in percent of sputum conversion between the two groups was tested by chi-square test. Difference in mean of sputum conversion time between the two groups was tested by t-test. Results: The mean serum vitamin D level in the intervention group (62.05±22.08) was higher than the control group (28.56±7.48) after the intervention, and it was statistically significant (p<0.001). After 56 days, all subjects in the vitamin D group experienced sputum conversion (100%) with a median sputum conversion time of 28 days, whereas 90% of subjects in the placebo group experienced sputum conversion with a median sputum conversion time of 48 days (p= 0.002). Conclusion: Adding vitamin D to anti-TB drug treatment effectively improves and accelerates sputum conversion of patients with tuberculosis acid-fast bacilli smear positive. Keywords: Vitamin D, sputum conversion, pulmonary tuberculosis Correspondence: Nita Andriani Lubis. Department of Health Analysis, School of Health Polytechnics Medan, North Sumatera. Jl. William Iskandar Pasar V Barat No. 6 Medan 20137, North Sumatera, Indonesia. Email: taufik.abay.mumtaz@gmail.com. Indonesian Journal of Medicine (2017), 2(3): 169-174 https://doi.org/10.26911/theijmed.2017.02.03.04

Knowledge and Practice of TB Patients on TB and its Treatment in Alamata District Tigray Region Northeast Ethiopia

Background: Tuberculosis (TB) leftovers the leading cause of death among a curable infectious disease, regardless of the availability of short-course therapy that can be both inexpensive and effective. The aim of the present study was to assess the level of knowledge about TB in clients who were initiating anti-TB drug treatment in Alamata District, northeast Ethiopia. Methods: A cross-sectional study was conducted in TB patients who were initiating anti-TB drug treatment in the district. Study participants were interviewed using a structured questionnaire to evaluate level of knowledge about TB. Data was entered and cleared using SPSS version 16. Results: A total of 200 study participants were interviewed, of whom 116 (58.0%) were male TB patients and 84 (42.0%) female TB patients. Among the study participants, 77.5% were new cases. 50% of them were extra pulmonary TB (EPTB) case, 23.5% were smear-positive pulmonary TB (SPPTB) cases and 26.5% were smearnegative PTB (SNPTB) cases and. The overall knowledge about TB of the study participants was 36.5%. Conclusions: There is significant knowledge breach in the study area among TB patients registered on treatment. Consolidation the awareness of TB patients using health education by health care providers on TB throughout the time of enrollment to treatment possibly will increase patients’ knowledge thus upgrading in treatment outcomes and overall TB control.

Adherence to Anti-tuberculosis treatment and treatment outcomes among tuberculosis patients in Alamata District, northeast Ethiopia.

BackgroundNon-adherence to tuberculosis (TB) treatment can result in an emergence of new strains, prolonged infectiousness, drug resistance and poor treatment outcomes. Thus, assessment of the level of adherence to anti-TB treatment, treatment outcomes and identifying factors associated with non-adherence and poor treatment outcomes are vital for improving TB treatment adherence and treatment outcomes in the study area. The main objectives of the current study were to assess the level of adherence to anti-TB treatment among patients taking anti-TB drug treatment and to identify factors associated with non-adherence. Whereas, the secondary objectives were to assess treatment outcomes and factors associated with poor treatment outcomes among TB patients previously treated at the health institutions of Alamata District, northeast Ethiopia.MethodsIn a health facility-based cross-sectional study, TB patients who were taking anti-TB drug treatment were interviewed using a structured questionnaire to evaluate level of adherence to anti-TB treatment. TB treatment outcomes were evaluated using data generated from a record review of previous TB patients who were treated at health facilities of Alamata District from January 2007 to June 2012. Adherence data and treatment outcomes data were computerized separately using Epi-Data version 3.1 and analyzed using STATA version 10.0.ResultsBetween November 2012 and January 2013, 116 (58.0 %) male TB patients and 84 (42.0 %) female TB patients were interviewed, of whom 77.5 % were new cases, 23.5 % were smear-positive pulmonary TB (SPPTB) cases, 26.5 % were smear-negative PTB (SNPTB) cases and 50.0 % were extra pulmonary (EPTB) cases. The overall adherence rate to anti-TB treatment was 88.5 %. The main reasons for the non-adherent patients were forgetting to take medication, being away from home, drug side effects, being unable to go to the health facilities on the date of appointment and being hospitalized. In the TB treatment outcomes component of the current study, records of 4,275 TB patients were reviewed and the overall treatment success rate was 90.1 %. Two-hundred fifteen (5.0 %) patients had unsuccessful treatment outcomes, of whom 76 (35.3 %) defaulted, 126 (58.6 %) died and 13 (6.1 %) had treatment failure. Significant predictors of unsuccessful treatment outcomes were being positive for human immunodeficiency virus (HIV) infection [adjusted odds ratio (aOR) = 2.1, 95 % CI 1.5–3.0], being SPPTB case (aOR = 3.4, 95 % CI 2.4–4.8), being SNPTB case (aOR = 2.0, 95 % CI 1.5–2.8)], and being re-treatment cases (aOR = 2.6, 95 % CI 1.5–3.7).ConclusionIn the present study area, there was a high level of adherence to anti-TB treatment and also a high TB treatment success rate. However, still further effort like health education to patient or family is needed to reduce those factors which affect adherence and treatment success rates in order to ensure higher rates of adherence and treatment success than the currently observed in the present study area.

Higher blood volumes improve the sensitivity of direct PCR diagnosis of blood stream tuberculosis among HIV-positive patients: an observation study.

BackgroundBlood stream tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) is common among HIV-positive patients, turning rapidly fatal unless detected and treated promptly. Blood culture is currently the standard test for the detection of MTB in whole blood but results take weeks; patients deteriorate markedly and often die before a diagnosis of blood stream TB is made. Rapid molecular tests on whole blood, with potential for same day diagnosis of blood stream TB usually show low sensitivity due to the problem of insufficient MTB DNA template when extraction is performed directly on low blood volumes. This study assessed the influence of blood volume on the sensitivity of a HyBeacon PCR assay-the FluoroType® MTB (Hain Lifescience, Nehren, Germany) on direct detection of MTB in whole blood.MethodsProspective recruitment of HIV-positive patients with clinical suspicion of blood stream TB but not on anti-TB or HIV drug treatment was done. Venous blood samples were collected and DNA extracted using the MolYsis (Molzym, Bremen, Germany) methods; for study A, from duplicate 1 ml (42 patients) and for study B (31 patients) from 9 ml EDTA blood samples. The FluoroType® MTB PCR assay targeting an IS6110 sequence was performed and results compared with blood culture.ResultsThe diagnostic sensitivity and specificity of the FluoroType® MTB PCR in study A was 33% and 97%, respectively. Corresponding values in study B were 71% and 96%, respectively. In both studies, one case each of blood culture-negative blood stream TB was detected with the FluoroType® MTB PCR assay. The median time to positivity of blood culture was 20.1 (range 12–32) for study A and 19.9 days (range 15–30) for study B.ConclusionLarger blood volumes (9 ml) improved and gave acceptable sensitivity of direct PCR diagnosis of blood stream TB.

Multidrug-resistant tuberculosis in Ethiopia: efforts to expand diagnostic services, treatment and care.

The emergence of drug-resistant tuberculosis (TB), particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, is a major public health problem. The purpose of this review is to describe the current status of MDR-TB and factors that increase the risk of this infection. We conducted a systematic review of the literature on MDR-TB in Ethiopia. Out of 766 articles, 23 were found to meet eligibility criteria and included in this review. Among the 23 papers, six of them reported high prevalence of MDR-TB in the range of 3.3%-46.3%. Likewise, two studies reported XDR-TB in the range of 1% - 4.4% in Ethiopia. The most powerful predictor of the emergence of MDR-TB reported in Ethiopia is previous exposure to anti-TB drug treatment. This review indicated that MDR-TB in Ethiopia is a serious public health problem that needs to be addressed urgently. Strengthening early case detection and proper treatment of drug-susceptible TB in accordance with World Health Organization (WHO) treatment guidelines to ensure adequate treatment success rates is critical. Consequently, efforts have been made to a rapidly increase MDR-TB diagnosis as well as the number of treatment sites to implement a directly observed treatment, short-course (DOTS) plus strategy to interrupt transmission of MDR-TB.

A meta-analysis of Drug resistant Tuberculosis in Sub-Saharan Africa: How Strongly Associated with previous Treatment and HIV Co-infection?

In Sub-Saharan Africa, the fight against tuberculosis (TB) has encountered a great challenge because of the emergence of drug resistant TB strains and the high prevalence of HIV infection. The aim of this meta-analysis was to determine the association of drug-resistant TB with anti-TB drug treatment history and HIV co-infection. After electronic based literature search in the databases of Medline, HINARI, EMBASE and the Cochrane library, article selection and data extraction were carried out. HIV co-infection and previous history of TB treatment were used as predictors for the occurrence of any anti-TB drug resistant or multiple drug resistant TB (MDR-TB). The risk ratios for each included study and for the pooled sample were computed using the random-effects model. Heterogeneity test, sensitivity analyses and funnel plots were also done. The pooled analysis showed that the risk of developing drug-resistant TB to at least one anti-TB drug was about 3 times higher in individuals who had a previous history of anti-TB treatment than new TB cases. The risk of having MDR-TB in previously anti-TB treated TB cases was more than 5-fold higher than that of new TB cases. Resistance to Ethambutol and Rifampicin was more than fivefold higher among the previously treated with anti-TB drugs. However, HIV infection was not associated with drug-resistant TB. There was a strong association of previous anti-TB treatment with MDR-TB. Primary treatment warrants special emphasis, and screening for anti-TB drugs sensitivity has to be strengthened.

Predictors of tuberculosis (TB) and antiretroviral (ARV) medication non-adherence in public primary care patients in South Africa: a cross sectional study

BackgroundDespite the downward trend in the absolute number of tuberculosis (TB) cases since 2006 and the fall in the incidence rates since 2001, the burden of disease caused by TB remains a global health challenge. The co-infection between TB and HIV adds to this disease burden. TB is completely curable through the intake of a strict anti-TB drug treatment regimen which requires an extremely high and consistent level of adherence.The aim of this study was to investigate factors associated with adherence to anti-TB and HIV treatment drugs.MethodsA cross-sectional survey method was used. Three study districts (14 primary health care facilities in each) were selected on the basis of the highest TB caseload per clinic. All new TB and new TB retreatment patients were consecutively screened within one month of anti-tuberculosis treatment. The sample comprised of 3107 TB patients who had been on treatment for at least three weeks and a sub-sample of the total sample were on both anti-TB treatment and anti-retro-viral therapy(ART) (N = 757). Data collection tools included: a Socio-Demographic Questionnaire; a Post-Traumatic-Stress-Disorder (PTSD) Screen; a Psychological Distress Scale; the Alcohol Use Disorder Identification Test (AUDIT); and self-report measures of tobacco use, perceived health status and adherence to anti-TB drugs and ART.ResultsThe majority of the participants (N = 3107) were new TB cases with a 55.9% HIV co-infection rate in this adult male and female sample 18 years and older. Significant predictors of non-adherence common to both anti-TB drugs and to dual therapy (ART and anti-TB drugs) included poverty, having one or more co-morbid health condition, being a high risk for alcohol mis-use and a partner who is HIV positive. An additional predictor for non-adherence to anti-TB drugs was tobacco use.ConclusionsA comprehensive treatment programme addressing poverty, alcohol mis-use, tobacco use and psycho-social counseling is indicated for TB patients (with and without HIV). The treatment care package needs to involve not only the health sector but other relevant government sectors, such as social development.

Dissecting the immunological, antimicrobial and clinical effects of vitamin D therapy in tuberculosis

Invited Commentary on ‘Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment’, Coussens et al., Proceedings of the National Academy of Sciences of the United States of America, 2012. ‘Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning’, Sir Winston Churchill, 1942. Vitamin D, in the form of cod-liver oil, was first used as a treatment for tuberculosis (TB) over a century ago. The more recent discovery that macrophages (the intracellular niche of M. tuberculosis) can synthesise the biologically active form of vitamin D – 1,25(OH)D3 – from its precursor, the association of vitamin D deficiency with TB disease,1 and the potent effects of 1,25(OH)D3 on mycobacterial killing in vitro through intracellular expression of the anti-microbial peptide LL-37,2 led to clinical trials of vitamin D as an adjunct to antimicrobial treatment of pulmonary TB. The results of the latest and most robust study were mixed, showing increased speed of sputum culture conversion only in the subset of vitamin D-treated patients with the tt genotype of the TaqI polymorphism of the Vitamin D Receptor.3 However, the investigators have now uncovered profound immunomodulatory effects of vitamin D therapy in their cohort.4 By comparing responses in those given anti-tuberculous therapy alone with those given adjunctive vitamin D, the effects of vitamin D on a range of circulating cytokines and chemokines during recovery from TB were compared. Vitamin D hastened the resolution of M. tuberculosis antigen-independent and antigen–dependent hypercytokineaemia in pulmonary TB; these effects were not restricted to patients with the tt TaqI polymorphism, but occurred also in patients with TT and Tt genotypes. Additionally, and in contrast to the original intention-to-treat analysis, an adjusted per-protocol re-analysis of the 96 patients who completed the full course of study medication showed a significant shortening of time to sputum smear conversion in the whole cohort with adjunctive vitamin D. Given the high efficacy of short course antimicrobial chemotherapy for drug-sensitive TB, detection of even a modest incremental effect of vitamin D on clinical endpoints is notable. Given that vitamin D hastened microbiological clearance, the accelerated resolution of inflammatory responses in patients receiving vitamin D is difficult to interpret. During effective anti-TB drug treatment, mycobacterial load and antigen load progressively decline and a range of M. tuberculosis-induced inflammatory responses wane correspondingly. Therefore, it is unclear whether the observed accelerated resolution of inflammatory responses is mediated directly by effects of vitamin D on the adaptive immune system, as concluded by the authors, or indirectly in response to an accelerated decline in bacillary burden and antigen load mediated by enhanced vitamin D-mediated innate intracellular killing of M. tuberculosis. This uncertainty may have clinical implications. If vitamin D directly attenuates inflammatory immune responses during TB treatment, it might have an adjunctive role in limiting immunopathology in certain clinical subtypes of TB, such as TB meningitis. This would be akin to adjunctive immunosuppressive corticosteroids, where net clinical benefit through suppression of immunopathology depends on the host genotype of key innate immune response genes.5 On the other hand, a number of case-series have posited an association between vitamin D therapy and hyper-inflammatory paradoxical ‘upgrading’ reactions during TB treatment.6 Future clinical trials of adjunctive vitamin D therapy should therefore correlate the kinetics of immune responses with clinical complications of immunopathology, such as paradoxical reactions, as well vitamin D receptor genotypes, although achieving the necessary sample size will be challenging. To unmask the full potential of adjunctive vitamin D therapy, future studies should focus on multidrug-resistant TB where the therapeutic effects of antituberculous antibiotics are blunted. Finally, the tantalising potential of vitamin D as preventative therapy, as suggested by a recent pilot study in Mongolia,7 must not be overlooked.

Genetic Interaction between NAT2, GSTM1, GSTT1, CYP2E1, and Environmental Factors Is Associated with Adverse Reactions to Anti-Tuberculosis Drugs

Adverse drug reactions (ADRs) associated with anti-tuberculosis (anti-TB) drug regimens have considerable impact on anti-TB treatment, potentially leading to unsuccessful outcomes. Nevertheless, the risk factors that play a role in anti-TB drug-induced ADRs are not well established. It is well documented that genetic polymorphisms in drug-metabolizing enzymes (DMEs) result in considerably complex variability in anti-TB drug disposition. In addition, the impact of pharmacogenetic variation on the metabolism of anti-TB drugs may be modifiable by environmental exposure. Thus, an assessment of pharmacogenetic variability combined with biomarkers of environmental exposure may be helpful for demonstrating the effect of the gene-environment interaction on susceptibility to ADRs induced by anti-TB drug therapy. The aim of the study was to investigate the impact of the interaction between environmental risk factors and pharmacogenetic polymorphisms in four common DMEs--N-acetyltransferase 2 (arylamine N-acetyltransferase) [NAT2], glutathione S-transferase theta 1 [GSTT1], glutathione S-transferase mu 1 [GSTM1], and cytochrome P450 2E1 [CYP2E1]--on commonly reported ADRs to first-line anti-TB drugs in 129 patients receiving homogeneous TB treatment. TB patients monitored during drug treatment were divided into subgroups according to the presence or absence of ADRs. Additionally, the patients' clinical and demographic characteristics were collected in order to identify the environmental factors that are potential triggers for ADRs induced by anti-TB drug treatment. Pharmacogenetic variability was determined by gene sequencing, TaqMan® assays, or polymerase chain reaction. The findings of this study suggest that the NAT2 slow acetylator haplotype, female sex, and smoking are important determinants of susceptibility to ADRs induced by anti-TB drugs. Patients carrying multiple, but not single, polymorphisms in the NAT2, GSTM1, GSTT1, and CYP2E1 genes were found to have an increased risk of ADRs, as revealed by gene-gene interaction analysis. Moreover, we also identified meaningful gene-environment interaction models that resulted in the highest levels of ADR risk. The study findings provide evidence of the clinical impact of the interaction between pharmacogenetic variability and environmental factors on ADRs induced by anti-TB drug therapy. Predictive pharmacogenetic testing and a comprehensive clinical history would therefore be helpful for identification and careful monitoring of patients at high risk of this complication.

Anti-phospholipid antibody levels as biomarker for monitoring tuberculosis treatment response

Standard methods to monitor tuberculosis (TB) treatment response rely on sputum microscopy and culture conversion. Alternatives to these methods are needed for those patients whose sputum tests are smear or culture negative. Here, we examine anti-phospholipid IgM antibody level changes as a biomarker for treatment response in smear positive TB patients. Serum samples were obtained from 40 pulmonary TB patients at the start and end of the intensive phase treatment (IPT) from the CDC-TB Trials Consortium randomized clinical trial in Kampala, Uganda. Samples were screened by ELISA for IgM levels against five phospholipids found in Mycobacterium tuberculosis and host cells. Lipid antigens included cardiolipin (CL), phosphatidyl inositol (PI), phosphatidyl ethanolamine (PE), phosphatidyl choline (PTC), and sphingolipid (SL). Levels of IgM against all phospholipids significantly decreased (p=0.034, 0.001, 0.008 0.008, 0.040, respectively) following anti-TB drug treatment in patients without lung cavitary disease at baseline. The mean sensitivity of this test in these patients was 83% when the IgM response to a single lipid antigen was used; it was >90% when responses to 2 or more lipids were assessed. In contrast, cavitary TB patients showed an overall IgM increase, with a significant rise against PE (p=0.025). There was no significant difference in the change in antibody levels between patients who remained culture-positive and those who culture-converted after 40 doses of drug therapy. The measurement of IgM anti-phospholipid antibodies may be a useful biomarker to monitor treatment response in non-cavitary TB patients.

Tuberculosis – An Under-appreciated Disease

Tuberculosis Worldwide Tuberculosis (TB, as usually abbreviated) is a major cause of morbidity and mortality in many countries, and a signifi cant public health problem worldwide. The World Health Organization (WHO) estimates that there are about 8.8 million new cases of TB and 1.6 million deaths from TB every year.1 Non-compliance with anti-TB drug treatment, or inappropriate treatment, or both, has led to one of the greatest challenge facing TB control programmes worldwide, i.e. drug-resistant tuberculosis. Drug-resistant TB is much more diffi cult and costly to treat than fully drug-susceptible TB. An estimated 490,000 cases of multi-drug resistant TB (MDR-TB), causing about 110,000 deaths, occur each year among both new and previously treated cases. These cases are resistant to rifampicin and isoniazid, the 2 most effective fi rst-line anti-TB drugs. The 2008 WHO Report on Anti-TB Drug Resistance stated that the world was experiencing the highest ever recorded rates of MDR-TB, with an average proportion among all TB cases of 5.3%. There were 14 geographic areas showing MDR-TB rates greater than 6% among new TB cases. These areas were mainly in countries of the former Soviet Union and in China. The highest rate of MDR-TB was reported in Baku City, the capital of Azerbaijan, where nearly a quarter of new TB cases were reported to be MDR-TB.2 The same 2008 WHO Report also indicated that cases of extensively drug-resistant TB (XDR-TB) have been reported in 45 countries, and emphasised that this phenomenon threatens to derail 10 years of progress in TB control. XDR-TB is TB that is resistant not just to rifampicin and isoniazid, but also to a fl uoroquinolone and to 1 of 3 injectable second-line anti-TB drugs (kanamycin, amikacin or capreomycin). XDR-TB is thus very diffi cult to treat, and the success rate of treatment is only 30% at best, in contrast to 50% to 70% for MDR-TB and over 95% success for pan-sensitive tuberculosis. Another major challenge has been the impact of the pandemic of human immunodefi ciency virus (HIV). HIV

Drug susceptibility profile of Mycobacterium tuberculosis isolated from HIV infected and uninfected pulmonary tuberculosis patients in Eastern India

HIV is driving the tuberculosis (TB) epidemic in many developing countries including India. This study was initiated to determine the drug resistance pattern of pulmonary TB among 200 HIV seropositive and 50 HIV negative hospitalized patients from different states of Eastern India. The TB positive isolates (120) were screened and characterized by conventional laboratory methods followed by first- and second-line drug susceptibility testing on Lowenstein-Jensen medium by the proportion method. The drug susceptibility testing showed 17.7% (16/90) and 6.6% (2/30) multidrug-resistant (MDR) TB for the HIV positive and HIV negative patients, respectively. 22.2% (4/18) of the isolated MDR-TB cases could be classified as extensively drug-resistant (XDR) TB isolates. 88.8% (16/18) of all the MDR-TB isolates and all XDR-TB isolates were screened from HIV patients. Five (27.7%) of the 18 MDR-TB isolates showed resistance to all the first-line drugs. Mortality rate among the XDR-TB isolates was as high as 75% (3/4). Patients with interrupted anti-TB drug treatment were the ones most affected. These findings are critical and the risk to public health is high, particularly with HIV infected patients.

Clinical efficacy of adefovir dipivoxil combined with anti-tuberculosis drugs inn treatment for chronic hepatitis B complicated with pulmonary tuberculosis

Objective It is purposed to evaluate clinical efficacy of adefovir dipivoxil combined with anti-tuberculosis (TB) drugs in treatment for chronic hepatitis B (HB) complicated with pulmonary TB. Methods Ninety-four eases of pulmonary TB complicated with chronic HB receiving anti-TB drug treatment at Liaocheng Hospital for Infectious Disease during September 2006 to September 2008 were divided into treatment and control groups matched on their pulmonary TB lesion, damage in liver function and HB virus (HBV) DNA load. Forty-seven cases in the treatment group were administered with anti-TB drugs, i.e., isoniazid (INH) 0. 3 g daily, rifapentine (RFT) 0.45 g twice a week, pyrazinamide (PZA) 1.5 g daily, streptomycin (SM) 0. 75 g daily or ethambutol (EMB) 0. 75 g daily, and regular liver-protection drags, as well as oral adefovir dipivoxil 10 mg daily for eight months, and another 47 cases in the control group were administered with the same anti-TB drugs and regular liver-protection drugs as the treatment group. Two to eight weeks after treatment, clinical symptoms, liver function, HBV DNA load, negative conversion of acid-fast staining bacteria in sputum smear, and absorption of pulmonary TB lesion were evaluated for all the patients in both groups. Data were analyzed with U-test and χ2-test, respectively. Results After treatment, damage in liver function worsened in three cases (6.4%), as compared to that in 47.3 percent of the control group (P<0.05). Clinical symptoms, including tiredness, loss of appetite, abdominal distension, uncomfortable in upper abdomen, and so on, appeared in three cases of the treatment group (6.4%) during anti-TB treatment, as compared to those in 18 cases of the control group (47.3%) (P<0.05). HBV DNA conversed to negative (less than 1.0×103 lg copies/ml) in 24 cases of the treatment group (51.1%), HBV load went down to 1.0×103-1.0×104 lg copies/ml in 23 cases (48. 9%), sputum smear bacteria conversed to negative in 41 cases (87. 2%) and pulmonary lesion absorbed in 45 cases (95.7%), all with statistically significance as compared to those in the control group (47. 3% , 0. 0% , 2. 6% , 39. 5% and 50. 0% , respectively, P <0. 05). Renal function was all in normal in both groups and no patient with drug resistant variant HBV was found during and after treatment, and no obviously adverse reaction was found in patients with adefovir dipivoxil. Conclusion Adefovir dipivoxil has a good safety and can reduce laver damage in anfi-TB drug treatment for patients of chronic hepatitis B complicated with pulmonary TB. Key words: Hepatitis B, chronic; Tuberculosis,pulmonary; Antitubercular agents

A comparative study on the adverse effects of two anti-tuberculosis drugs regimen in initial two-month treatment period

Tuberculosis (TB) is a leading cause of death throughout the world and Bangladesh stands 4th among high burden countries. Treatment of TB hampered with poor patient compliance and intolerance at least partly due to the adverse drug reactions. A prospective longitudinal non-randomized case study was conducted on 64 Hospital admitted patients diagnosed as primary (category I) and resistant or treatment failure (category II) to compare adverse effects between two anti-TB drug treatment regimen based on diagnostic category. Category I received four drug (rifampicin, isoniazid, ethambutol, pyrazinamide) and category II received five drug (rifampicin, isoniazid, ethambutol, pyrazinamide, sparfloxacin) combination treatments for initial 2 months under DOTS during the period of July 2004 to July 2005. Adverse effect parameters e.g. gastrointestinal disturbances, arthralgia, hepatic dysfunction and renal impairment were estimated before, two and eight weeks after initiation of treatment. Predisposing risk factors for adverse effects e.g. age, sex, nutritional status, associated disease, habits were also analyzed. In our study, 76.5% of total patients experienced some sorts of adverse effects. In 4- and 5-drug regimen groups’ adverse reaction were observed in 50 and 95% of patients respectively. Serum bilirubin, SGPT, creatinine did not change in neither of the treated group while alkaline phosphatase tended to decrease and uric acid to increase. No disease was established to be risk factor for drug intolerance.

Vaccination-relatedMycobacterium bovisBCG Infection

Vaccination-related<i>Mycobacterium bovis</i>BCG Infection

Hepatoprotective Effect of Liv. 100, a Polyherbal Formulation, on Mitochondrial Enzymes in Anti-Tubercular Drug-Induced Liver Damage in Rats.

We studied the anti-hepatotoxic potential of Liv.100, a herbal formulation, on anti-tubercular (anti-TB) drugs [isoniazid (INH), rifampicin (RMP), and pyrazinamide (PZA)]-induced mitochondrial damage in rat liver. Liv.100 (400mg/kg body wt./day, orally) was administered simultaneously with anti-TB drugs for 6 weeks. Activities of TCA cycle enzymes (succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase, and α-ketoglutarate dehydrogenase) and respiratory marker enzymes (cytochrome c oxidase, NADH dehydrogenase) and levels of mitochondrial lipid peroxidation in liver were determined. Activities of TCA cycle enzymes and respiratory marker enzymes were significantly lower upon anti-TB drug treatment than those of normal controls. Mitochondrial lipid peroxidation was found to be increased when compared with the normal control value. This indicates impaired function of hepatic mitochondria in anti-TB drug-induced hepatocellular damage. In our present study, Liv.100 co-administration significantly reduced the anti-TB drug-induced alterations in the level of lipid peroxide and activities of TCA cycle enzymes and respiratory marker enzymes in liver mitochondria. The mechanism of action of Liv.100 is probably due to its antioxidant nature against anti-TB drug-induced lipid peroxidation, which is mainly responsible for the inhibition of these enzyme activities.

The Changes in Levels of Serum Alanine Aminotransferase (ALT) During Anti Tubercular Treatment With 4FDC (Fixed Drug Combination)

Tuberculosis (TB) is emerging as a major public health problem in Bangladesh, which now has the fifth highest burden of TB cases globally. Treatment of TB hampered with poor patient compliance and intolerance at least partly due to the adverse drug reactions, one of which is hepatotoxicity. Serum alanine aminotransferase level is an important indicator of such condition and impacts upon the continuation of anti tubercular treatment. A prospective randomized case study was conducted among 62 patients diagnosed as pulmonary tuberculosis receiving category I anti-TB drug treatment regimen in the DOTS (Direct observation therapy short-course) providing centers at Pabna district under DOTS during the period of July 2004 to July 2006. Category I comprised of four drugs (Rifampicin, Isoniazid, Ethambutol, Pyrazinamide) combination patients treated for initial 2 months, serum alanine aminotransferase levels were estimated at the first and fourth week of the treatment. Serum billirubin, HBsAg, Anti-HCV was also done to exclude some other liver diseases. 14(22.58%) patients were found to have no significant change, 34(54.84%) patients had their levels in the upper limits, 13(20.97%) patients had their levels in-between the upper limit and twice of the upper limit, while only 1(1.6%) patient crossed the level twice the upper limit. DOI: 10.3329/taj.v22i1.5029 TAJ 2009; 22(1): 106-110